BEHAVIORAL PHARMACOLOGY & TOXICOLOGY OF ABUSED INHALANTS

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The purpose of the research proposed in this request for an ADAMHA RSDA (Level II) is to advance the behavioral pharmacology and toxicology of inhalants. The scientific content of the proposal grows from a NIDA grant in progress for fourteen years that has just been moved to the NYU Medical Center. Except for the opportunities to gain new competencies and to profit from the unique research potential of my new environment, the specific aims of the research program remains the same: The development of models of inhalant abuse will provide techniques that: (1) permit assessment of the relative abuse potential of solvents and anesthetics; (2) permit specification of nontoxic levels of solvent exposure and the recommendation of industrial exposure limit values; (3) permit comparison of the strength of inhalant-maintained drug-seeking behavior with the strength of behavior maintained by other drugs of abuse. The proposed program will proceed in parallel phases: 1) Solvent self-administration by the monkey. Concentration- and duration-effect curves will be determined for inhalants such as alkyl benzenes (e.g. toluene), ketones, and aliphatic alcohols. Schedules of reinforcement will be examined to determine the effectiveness of these agents as reinforcers. Inhalant blood levels will be determined. 2) Aversive properties of inhaled substances. We will generate performances maintained by the termination of noxious inhalants. Initial aversiveness may play an important role in determining abuse potential. Techniques to make volatile materials aversive are of paramount importance, and could bear directly on product formulation. 3) Effects of organic solvents on performance. Inhaled materials induce behavioral toxicity that can be measured by using schedule-controlled behavior. Concentration- effect curves of several agents will be obtained to determine how concentrations that maintain self-administration are related to those that affect other performances. This helps characterize their pharmacologic profiles and, with both self-administration and pharmacokinetic data, helps us understand the determinants of inhalant abuse.